The present invention relates to pyrimidines of formula I 
in which
R1 represents hydrogen or
C1-C10-alkyl, C1-C10-haloalkyl, C2-C6-alkenyl, C2-C6-alkynyl, C4-C8-alkadienyl, C1-C10-alkoxy, C3-C8-cycloalkyl, phenyl, or
5- or 6-membered heteroaryl or 5- or 6-membered heterocyclyl, containing one to four nitrogen atoms or one to three nitrogen atoms and one sulfur or oxygen atom, or
tri-C1-C6-alkyl-silyl, formyl or C1-C10-alkoxycarbonyl;
wherein R1 groups are unsubstituted or substituted by one to three groups Ra 
Ra halogen, nitro, cyano, hydroxy or
C1-C10-alkyl , C3-C6-cycloalkyl, C3-C6-cycloalkenyl, C1-C10-haloalkyl, C3-C6-halocycloalkyl, C1-C10-alkoxy, C1-C10-haloalkoxy, C1-C10-haloalkoxy, C1-C6-alkoxycarbonyl, tri-C1-C4-alkylsilyl, phenyl, halo- or dihalo-phenyl or 5- or 6-membered heteroaryl, containing one to four nitrogen atoms or one to three nitrogen atoms and one sulfur or oxygen atom;
R2 represents phenyl, C3-C6-cycloalkyl or 5- or 6-membered heteroaryl, containing one to four nitrogen atoms or one to three nitrogen atoms and one sulfur or oxygen atom, which are unsubstituted or substituted by one to three groups Ra;
R3 represents hydrogen, halogen or
C1-C10-alkyl, C1-C10-alkoxy, C1-C10-alkylthio, C1-C10-alkylamino or di-C1-C10-alkylamino; which are unsubstituted or substituted by one to three groups Ra;
R4 represents hydrogen or
C1-C10-alkyl, C2-C6-alkenyl or C2-C6-alkynyl; which are unsubstituted or substituted by one to three groups Ra; and
X represents O, S, NR5 or a single bond, wherein R5 represents hydrogen or C1-C10-alkyl; or
R1 and R5 together with the interjacent nitrogen atom form a heterocyclic ring.
Moreover, the invention relates to processes and intermediates for preparing these compounds, to compositions comprising them and to their use for controlling harmful fungi.
In Vestn. Slov. Kem. Drus. (1986), 33(3), 353-66 (ISSN: 0560-3110, CAN 107:39701) it is disclosed that the reaction of N-pyrimid-2-ylformamide oximes with N,N-dimethylformamide diethyl acetal yields 2-(N-cyano-N-ethylamino)pyrimidines. In J. Org. Chem. 39 (9) 1256-1252 (1974) N-glycosylated 2-(N-cyanoamino) pyrimidines are disclosed and in U.S. Pat. No. 4,711,959 a process for the preparation of 2-(N-cyanoamino)pyrimidines is described.
It is an object of the present invention to provide fungicidal compounds having improved activity.
We have found that this object is achieved by the compounds defined at the outset. Furthermore, we have found processes for their preparation, compositions comprising them and methods for controlling harmful fungi using the compounds I.
Compounds of formula I wherein R4 is an optionally substituted alkyl, alkenyl or alkynyl group as defined above may be obtained by treating a compound of the formula II 
in which R1 through R3 and X are as defined in formula I; with a strong base and an alkylation agent of formula III
R4xe2x80x94Yxe2x80x83xe2x80x83III
in which R4 is C1-C6-alkyl, C1-C6-alkenyl or Cl-C6-alkynyl; which are unsubstituted or substituted by one to three groups Ra, and Y represents a nucleophilic replaceable leaving group, preferably a halogen atom, in particular a iodine atom
Compounds of formula II are known for example from U.S. Pat. No. 5,593,996, WO-A 98/46608, FR-A 2,765,875, WO-A 99/41255 or WO-A 99/48893.
The reaction between the triazolopyrimidines of formula II, the strong base and the alkylation agent of formula III is preferably carried out in the presence of an inert solvent. Suitable solvents include ethers, such as dioxane, diethyl ether and tetrahydrofuran, halogenated hydrocarbons such as dichloromethane, amides, such as dimethylformamide or N-methylpyrrolidone and aromatic hydrocarbons, for example toluene or mixtures of these solvents. The reaction is suitably carried out at a temperature in the range from xe2x88x9278xc2x0 C. to 100xc2x0 C., the preferred reaction temperature is from 10xc2x0 C. to 80xc2x0 C., particular at ambient temperature.
Suitable strong bases include metal hydrides, such as sodium hydride, potassium hydride or calcium hydride, and metal amides, such as sodium amide, potassium amide, lithium diisopropylamide or potassium hexamethyldisilazide, and metal alkanes such as methyllithium, n-butyllithium or tert-butyllithium.
Furthermore, the compounds of formula I wherein R4 is an optionally substituted alkyl, alkenyl or alkynyl group may be prepared by reacting a N-pyrimid-2-ylformamide oxime of formula IV 
in which R1 through R3 and X are as defined in formula I; with a N,N-dimethylformamide dialkyl acetate of formula V 
in which R4 is is C1-C6-alkyl, C1-C6-alkenyl or C1-C6-alkynyl; which are unsubstituted or substituted by one to three groups Ra.
The reaction between the compounds of formula IV and the compounds of formula v can be carried out analogosly to the reaction described in Vestn. Slov. Kem. Drus. (1986), 33(3), 353-66.
Compounds of formula I wherein R4 is hydrogen can preferably be prepared by treating sulfones of formula VI 
in which R1 through R3 and X are as defined in formula I and R6 is C1-C6-alkyl or C1-C6-haloalkyl; with cyanamide or with a metal salt of cyanamide. The use of a base and/or a solvent can be advantageous.
This process is preferably carried out in the presence of an inert solvent. Suitable solvents include aromatic hydrocarbons, such as, for example toluene or xylene, chlorinated hydrocarbons, such as, for example methylene chloride, chloroform, a chlorobenzene, ketones, such as, for example acetone, methyl ethyl ketone, methyl isopropyl ketone or methyl isobutyl ketone, nitriles, such as, for example acetonitrile or propionitrile ethers, such as, for example diethyl ether, diisopropyl ether, methyl tert-butylether, dimethoxyethane, tetrahydrofuran or dioxane, amides, such as, for example, dimethylacetamide or diethylacetamide, sulfoxides, such as, for example dimethylsulfoxide or sulfolane, or mixtures thereof.
The use of a base can be advantageous in this reaction. Suitable bases include alkali metal hydrides and earth alkaline metal hydrides, such as, for example, sodium, potassium or calcium hydrides, alkali metal hydroxides and alkaline earth metal hydroxides, such as, for example, sodium, potassium or calcium hydroxides, alkali metal carbonates and alkaline earth metal carbonates, such as, for example sodium carbonate, potassium carbonate or calcium carbonate, alkali metal bicarbonates and alkaline earth metal bicarbonates, such as sodium bicarbonate, potassium bicarbonate or calcium bicarbonate, metal amides, such as, for example sodium amide, potassium amide, lithium diisopropylamide or potassium hexamethyldisilazide, metal alkanes, such as for example methyl lithium, n-butyl lithium or tert-butyl lithium or aprotic amines, such as, for example pyridine, tributylaine, N,N-dimethylbenzylamine or diazobicycloundecene.
Various qualities of cyanamide may be employed for the process. The use of an aqueous solution of cyanamide may be preferred for practical reasons. The use of metal salts of cyanamide, potassium cyanamide, dipotassium cyanamide or calcium cyanamide is also possible.
Dependant an the used cyanamide or salt of, cyanamide and dependant on the base an appropriate solvent is employed.
The reaction is suitable carried out at a temperature in the range from xe2x88x9278xc2x0 C. to reflux temperature, the preferred reaction temperature is from 0xc2x0 C. to 150xc2x0 C., particular at ambient temperature.
In general 1 to 3 equivalents, preferably 1.5 to 2.5 equivalents of base are employed per equivalent of sulfone of the formula VI.
Generally 2 to 6 equivalents, preferably 3 to 5 equivalents of cyanamide or salt of cyanamide are employed per equivalent of the sulfone of the general formula VI.
Compounds of formula I wherein R4 is is C1-C6-alkyl, C1-C6-alkenyl or C1-C6-alkynyl which are unsubstituted or substituted by one to three groups Ra may be prepared by alkylation of compounds of formula I wherein R4 is hydrogen with an alkylation agent of formula III.
The use of a base can be advantageous in this reaction. Suitable bases include alkali metal hydrides and earth alkaline metal hydrides, such as, for example, sodium, potassium or calcium hydrides, alkali metal hydroxides and alkaline earth metal hydroxides, such as, for example, sodium, potassium or calcium hydroxides, alkali metal carbonates and alkaline earth metal carbonates, such as, for example sodium carbonate, potassium carbonate or calcium carbonate, alkali metal bicarbonates and alkaline earth metal bicarbonates, such as sodium bicarbonate, potassium bicarbonate or calcium bicarbonate, metal amides, such as, for example sodium amide, potassium amide, lithium diisopropylamide or potassium hexamethyldisilazide, metal alkanes, such as for example methyl lithium, n-butyl lithium or tert-butyl lithium or aprotic amines, such as, for example pyridine, tributylaine, N,N-dimethylbenzylamine or diazobicycloundecene.
The alkylation is preferably carried out in the presence of an inert solvent. Suitable solvents include aromatic hydrocarbons, such as, for example toluene or xylene, chlorinated hydrocarbons, such as, for example methylene chloride, chloroform, a chlorobenzene, ketones, such as, for example acetone, methyl ethyl ketone, ethyl isopropyl ketone or methyl isobutyl ketone, nitriles, such as, for example acetonitrile or propionitrile ethers, such as, for example diethyl ether, diisopropyl ether, methyl tert-butylether, dimethoxyethane, tetrahydrofuran or dioxane, amides, such as, for example, dimethylacetamide or diethylacetamide, sulfoxides such as, for example dimethylsulfoxide or sulfolane, or mixtures thereof.
The reaction is suitably carried out at a temperature in the range from xe2x88x9278xc2x0 C. to reflux temperature, the preferred reaction temperature is 0xc2x0 C. to 150xc2x0 C., particular ambient temperature. In general 0.8 to 5 equivalents, preferably 0.8 to 4.5 equivalents of the alkylation agent of the formula III are employed per equivalent of the compound of formula I.
Usually 0.8 to 3 equivalents, preferably 0.8 to 4.5 equivalents of base are employed per equivalent of the compound of formula I.
It is also possible to prepare compounds of formula I wherein R4 is is C1-C6-alkyl, C1-C6-alkenyl or C1-C6-alkynyl which are unsubstituted or substituted by one to three groups Ra by reacting a sulfone of formula VI 
in which R1 through R3 and X are as defined in formula I and R6 is C1-C6-alkyl or C1-C6-haloalkyl; with an alkylated cyanamide of formula VII 
wherein R4 is is C1-C6-alkyl, C1-C6-alkenyl or C1-C6-alkynyl which are unsubstituted or substituted by one to three groups Ra. The use of a base and/or a solvent can be advantageous.
Suitable bases and solvents are such as listed at the reaction with cyanamide.
The reaction is suitable carried out at a temperature in the range of from xe2x88x9278xc2x0 C. to reflux temperature, the preferred reaction temperature is from 0xc2x0 C. to 150xc2x0 C., particular at ambient temperature.
The reaction is in general carried out under usual pressure.
In general 1 to 3 equivalents preferably 1.5 to 2.5 equivalents of base are employed per equivalent of the sulfone of formula VI.
Usually 2 to 6 equivalents, preferably 3 to 5 equivalents of alkylated cyanamide of formula VII are employed per equivalents of the sulfone of formula VI.
Sulfones of the formula VI are obtained by reacting 2-thiopyrimidinederivatives of the formula VIII 
in which the variables are as defined in formula VI; with oxidizing agents, such as, for example m-chloroperbenzoic acid, per acetic acid, trifluoro per acetic acid, chlorine water, hypochorous acid or metal salt solutions thereof in water or hydrogen peroxide, if appropriate in presence of a catalyst, such as for example wolframate.
If appropriate solvents, such as for example, methylene chloride, chloroform, carbontetrachloride, 1,2-dichloroethane or chlorobenzene are used at temperatures of xe2x88x9220xc2x0 C. to reflux.
The 2-thiopyrimidine derivatives of the formula VIII may be obtained when 6-halo-2-thiopyrimidines of formula IX 
in which the substituents are as before mentioned and xe2x80x9cHalxe2x80x9d denotes halogen; are reacted with a nucleophile of formula X
Hxe2x80x94Xxe2x80x94R1xe2x80x83xe2x80x83X
wherein R1 and X are as defined in formula I, if appropriate in the presence of a suitable base and if appropriate in an organic solvent. The solvents and bases employed are similar to those mentioned for the preparation of the compounds of formula I.
6-halo-2-thiopyrimidines of formula IX are known in the art or may be prepared according following reaction sequence: 
(R2, R3 and R6 are as defined above and R is an alkyl group) The reaction conditions are in general known in the art.
Base catalyzed reaction of dialkylmalonate with thiourea affords 2-thiobarbituric acid XII which may be selectively alkylated on sulfur to yield XIII.
Halogenation, preferably chlorination or bromination, especially chlorination, with for example phophorous oxychloride or phosphorous oxybromide in the presence of a tertiary amine base then affords the dihalo derivative XIV.
Subsequent introduction of the radical R3, if appropriate, via nucleophilic substitution affords the 6-halo-2-thiopyrimidine of formula IX.
Sulfones of formula VI and 2-thiopyrimidine derivatives of formula VIII are novel,
In the symbol definitions given in the formulae above, collective terms were used which generally represent the following substituents:
halogen: fluorine, chlorine, bromine and iodine;
xe2x80x94C1-C6-alkyl and the alkyl moieties of C1-C6-alkoxy, C1-C6-alkylthio, C1-C6-alkylamino, di-C1-C6-alkylamine or
C1-C6-alkoxycarbonyl: saturated, straight-chain or branched hydrocarbon radicals having 1 to 6 carbon atoms, preferrably C1-C4-alkyl, such as methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl; or pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-di-methylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl; preferrably ethyl or methyl;
xe2x80x94C1-C6-haloalkyl and the haloalkyl moieties of C1-C6-haloalkoxy: straight-chain or branched alkyl groups having 1 to 6 carbon atoms (as mentioned above), where the hydrogen atoms in these groups may be partially or fully replaced by halogen atoms as mentioned above, for example C1-C2-haloalkyl, such as chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1-bromoethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl and pentafluoroethyl; preferrably 2,2,2-trifluoroethyl or 1,1,1-trifluoroprop-2-yl;
xe2x80x94C3-C8-cycloalkyl: monocyclic, saturated hydrocarbon radicals having 3 to 6 or 8 carbon ring members, for example cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl, preferably 5 to 7 carbon atoms, in particular cyclopentyl being optionally substituted by one or more halogen atoms, nitro, cyano, C1-C6-alkyl or C1-C6-alkoxy.
xe2x80x94C2-C4-alkenyl: unsaturated, straight-chain or branched hydrocarbon radicals having 2 to 4 carbon atoms and a double bond in any position, for example ethenyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl and 2-methyl-2-propenyl; preferrably allyl or 2-methylallyl.
xe2x80x94C2-C4-haloalkenyl and the haloalkenyl moieties of C2-C4-haloalkenyloxy: unsaturated, straight-chain or branched hydrocarbon radicals having 2 to 4 carbon atoms and a double bond in any position (as mentioned above), where the hydrogen atoms in these groups may be partially or fully replaced by halogen atoms as mentioned above, in particular by fluorine, chlorine and bromine;
xe2x80x94C2-C4-alkynyl: straight-chain or branched hydrocarbon radicals having 3 to 4 carbon atoms and a triple bond in any position, for example ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl and 1-methyl-2-propynyl;
xe2x80x94C3-C4-haloalkynyl and the haloalkynyl moieties of C2-C4-haloalkynyloxy: unsaturated, straight-chain or branched hydrocarbon radicals having 2 to 4 carbon atoms and a triple bond in any position (as mentioned above), where the hydrogen atoms in these groups may be partially or fully replaced by halogen atoms as mentioned above, in particular by fluorine, chlorine and bromine;
5-membered heteroaryl, containing one to four nitrogen atoms or one to three nitrogen atoms and one sulfur or oxygen atom: 5-membered heteroaryl groups which, in addition to carbon atoms, may contain one to four nitrogen atoms or one to three nitrogen atoms and one sulfur or oxygen atom as ring members, for example 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyrrolyl, 3-pyrrolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-imidazolyl, 4-imidazolyl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,2,4-thiadiazol-3-yl, 1,2,4-thiadiazol-5-yl, 1,2,4-triazol-3-yl, 1,3,4-oxadiazol-2-yl, 1,3,4-thiadiazol-2-yl and 1,3,4-triazol-2-yl;
6-membered heteroaryl, containing one to four nitrogen atoms: 6-membered heteroaryl groups which, in addition to carbon atoms, may contain one to three or one to four nitrogen atoms as ring members, for example 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-pyrazinyl, 1,3,5-triazin-2-yl and 1,2,4-triazin-3-yl; preferred hetaryl moieties are pyridyl, pyrimidyl, pyrazolyl or thienyl.
5- or 6-membered heterocyclyl, containing one to four nitrogen atoms or one to three nitrogen atoms and one sulfur or oxygen atom, for example 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydrothienyl, 3-tetrahydrothienyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 3-isoxazolidinyl, 4-isoxazolidinyl, 5-isoxazolidinyl, 3-isothiazolidinyl, 4-isothiazolidinyl, 5-isothiazolidinyl, 3-pyrazolidinyl, 4-pyrazolidinyl, 5-pyrazolidinyl, 2-oxazolidinyl, 4-oxazolidinyl, 5-oxazolidinyl, 2-thiazolidinyl, 4-thiazolidinyl, 5-thiazolidinyl, 2-imidazolidinyl, 4-imidazolidinyl, 1,2,4-oxadiazolidin-3-yl, 1,2,4-oxadiazolidin-5-yl, 1,2,4-thiadiazolidin-3-yl, 1,2,4-thiadiazolidin-5-yl, 1,2,4-triazolidin-3-yl, 1,3,4-oxadiazolidin-2-yl, 1,3,4-thiadiazolidin-2-yl, 1,3,4-triazolidin-2-yl, 2,3-dihydrofur-2-yl, 2,3-dihydrofur-3-yl, 2,4-dihydrofur-2-yl, 2,4-dihydrofur-3-yl, 2,3-dihydrothien-2-yl, 2,3-dihydrothien-3-yl, 2,4-dihydrothien-2-yl, 2,4-dihydrothien-3-yl, 2-pyrrolin-2-yl, 2-pyrrolin-3-yl, 3-pyrrolin-2-yl, 3-pyrrolin-3-yl, 2-isoxazolin-3-yl, 3-isoxazolin-3-yl, 4-isoxazolin-3-yl, 2-isoxazolin-4-yl, 3-isoxazolin-4-yl, 4-isoxazolin-4-yl, 2-isoxazolin-5-yl, 3-isoxazolin-5-yl, 4-isoxazolin-5-yl, 2-isothiazolin-3-yl, 3-isothiazolin-3-yl, 4-isothiazolin-3-yl, 2-isothiazolin-4-yl, 3-isothiazolin-4-yl, 4-isothiazolin-4-yl, 2-isothiazolin-5-yl, 3-isothiazolin-5-yl, 4-isothiazolin-5-yl, 2,3-dihydropyrazol-1-yl, 2,3-dihydropyrazol-2-yl, 2,3-dihydropyrazol-3-yl, 2,3-dihydropyrazol-4-yl, 2,3-dihydropyrazol-5-yl, 3,4-dihydropyrazol-1-yl, 3,4-dihydropyrazol-3-yl, 3,4-dihydropyrazol-4-yl, 3,4-dihydropyrazol-5-yl, 4,5-dihydropyrazol-1-yl, 4,5-dihydropyrazol-3-yl, 4,5-dihydropyrazol-4-yl, 4,5-dihydropyrazol-5-yl, 2,3-dihydrooxazol-2-yl, 2,3-dihydrooxazol-3-yl, 2,3-dihydrooxazol-4-yl, 2,3-dihydrooxazol-5-yl, 3,4-dihydrooxazol-2-yl, 3,4-dihydrooxazol-3-yl, 3,4-dihydrooxazol-4-yl, 3,4-dihydrooxazol-5-yl, 3,4-dihydrooxazol-2-yl, 3,4-dihydrooxazol-3-yl, 3,4-dihydrooxazol-4-yl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 1,3-dioxan-5-yl, 2-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl, 3-hexahydropyridazinyl, 4-hexahydropyridazinyl, 2-hexahydropyrimidinyl, 4-hexahydropyrimidinyl, 5-hexahydropyrimidinyl, 2-piperazinyl, 1,3,5-hexahydro-triazin-2-yl and 1,2,4-hexahydrotriazin-3-yl; preferred heterocyclyl groups are pyrrolidinyl, pyrazolidinyl, piperidinyl, piperazinyl or morpholin-4-yl.
The particularly preferred embodiments of the intermediates with respect to the variables correspond to those of the radicals R1, R2, R3 and R4 of formula I.
With respect to their intended use, preference is given to pyrimidines of formula I having the following substituents, where the preference is valid in each case on its own or in combination:
Compounds of formula I are preferred wherein R1 denotes C3-C10-alkyl, C3-C8-cycloalkyl, C3-C8-cycloalkyl-C1-C6-alkyl, C1-C10-haloalkyl or phenyl being optionally substituted by one to three halogen atoms or C1-C10-alkyl or C1-C10-alkoxy.
Furthermore, particular preference is given to compounds I in which R1 is C1-C10haloalkyl, preferably polyfluorinated alkyl, in particular 2,2,2-trifluoroethyl, 2-(1,1,1-trifluoropropyl) or 2-(1,1,1-trifluorobutyl).
Likewise, particular preference is given to compounds I in which R1 denotes optionally substituted C3-C8-cycloalkyl, preferably cyclopentyl or cyclohexyl.
Moreover, particular preference is given to compounds I in which R2 represents phenyl being substituted by 2 or 3 substituents. Most preferred at least one of these substituents is attached in the 2-position with respect to the point of attachment to the pyrimidine moiety. Such substituents preferably include halogen or alkoxy.
Furthermore, particular preference is given to compounds I in which R2 represents a phenyl group of formula 
wherein L1 through L4 each independently represent hydrogen, fluorine, chlorine or methoxy, in particular L1 represents fluorine or chlorine, L2 and L4 each independently represent hydrogen, fluorine or chlorine, and L3 represents hydrogen, fluorine, chlorine or methoxy.
Particular preference is given to compounds of formula I in which R3 is chlorine.
Besides, particular preference is given to compounds I in which R4 represents hydrogen, C1-C6-alkyl, C2-C6-alkenyl or C2-C6-alkynyl; or phenyl-C1-C4-alkyl, wherein the phenyl ring may be substituted by one or two halogen atoms.
Likewise, particular preference is given to compounds I in which R4 is hydrogen, C1-C6-alkyl or benzyl, especially C1-C6-alkyl.
Particular preference is given to compounds I in which X is NR5 and R5 is hydrogen, C1-C10-alkyl or C1-C10-haloalkyl, in particular hydrogen.
Besides, particular preference is given to compounds I in which R5 represents C1-C6-alkyl, especially hydrogen or methyl.
Particular preference is also given to compounds I in which X represent NR5 and R1 together with the interjacent nitrogen atom form an optionally substituted heterocyclic ring, preferably an optionally substituted 3- to 7-membered heterocyclic ring, in particular a pyrrolidine, piperidine, tetrahydropyridine, in particular 1,2,3,6-tetrahydropyridine or azepane ring which is optionally substituted by one or more C1-C10-alkyl groups.
Most preferred are the compounds of formula IA 
in which R1 to R5 have the meaning given in formula I, L1 is F or Cl, L2 and L4 each independently are H, F or Cl, and L3 is H, F, Cl or OCE3.
Likewise, most preferred are the compounds wherein R3 is chlorine, X is NH, R4 is C1-C6-alkyl, C2-C6-alkenyl or C2-C6-alkynyl, especially C1-C6-alkyl, R2 represents phenyl optionally substituted by one or more fluorine and/or chlorine atoms and/or methoxy groups.
Particularly preferred are following compounds of formula IA:
Included in the scope of the present Invention are (R) and (S) isomers of compounds of general formula I having a chiral center and the racemates thereof, and salts, N-Oxides and acid addition compounds.
The compounds according to formula I are superior through their valuable fungicidal properties, in particular their enhanced systemicity. For example, they can be used in agriculture or related fields for the control of phytopathogenic fungi such as Alternaria solani, Botrytis cinerea, Cercospora beticola, Cladosporium herbarum, Corticium rolfsi, Erysiphe graminis, Helminthosporium tritici repentis, Lepfosphaeria nodorum, Micronectriella nivalis, Monilinia fructigena, Mycosphaerella ligulicola, Mycosphaerella pinodes, Rhizotonia solani, Sclerotinia sclerotiorum, Uncinula necator and Venturia inaequalis, in particular Pyricularia oryzae, Rhizoctonia solani and Venturia inaequalis. The compounds of formula I according to the invention possess a high fungicidal activity within a wide concentration range.
Due to excellent activity, the compounds of formula I may be used in cultivation of all plants where infection by phytopathogenic fungi is not desired, e.g. cereals, solanaceous crops, vegetables, legumes, appies, vine.
The Invention further provides a fungicidal composition which comprises an active ingredient, which is at least one compound of formula I as defined above, and one or more carriers. A method of making such a composition is also provided which comprises bringing a compound of formula I as defined above into association with the carrier(s). Such a composition may contain a single active ingredient or a mixture of several active ingredients of the present Invention. It is also envisaged that different isomers or mixtures of isomers may have different levels or spectra of activity and thus compositions may comprise individual isomers or mixtures of isomers.
A composition according to the Invention preferably contains from 0.5% to 95% by weight (w/w) of active ingredient.
A carrier in a composition according to the Invention is any material with which the active ingredient is formulated to facilitate application to the locus to be treated, which may for example be a plant, seed, soil, or water in which a plant grows, or to facilitate storage, transport or handling. A carrier may be a solid or a liquid, including material which is normally a gas but which has been compressed to form a liquid.
The compositions may be manufactured into e.g. emulsion concentrates, solutions, oil in water emulsions, wettable powders, soluble powders, suspension concentrates, dusts, granules, water dispersible granules, micro-capsules, gels, tablets and other formulation types by well established procedures. These procedures include intensive mixing and/or milling of the active ingredients with other substances, such as fillers, solvents, solid carriers, surface active compounds (surfactants), and optionally solid and/or liquid auxiliaries and/or adjuvants. The form of application such as spraying, atomizing, dispersing or pouring may be Chosen like the compositions according to the desired objectives and the given circumstances.
Solvents may be aromatic hydrocarbons, e.g. Solvess(copyright) 200, substituted naphthalenes, phthalic acid esters, such as dibutyl or dioctyl phthalate, aliphatic hydrocarbons, e.g. cyclohexane or Paraffins, alcohols and glycols as well as their ethers and esters, e.g. ethanol, ethyleneglycol mono- and dimethyl ether, ketones such as cyclohexanone, strongly polar solvents such as N-methyl-2-pyrrolidone, or xcex3-butyrolactone, higher alkyl pyrrolidones, e.g. n-octylpyrrolidone or cyclohexylpyrrolidone, epoxidized plant oil esters, e.g. methylated coconut or soybean oil ester and water. Mixtures of different liquids are often suitable.
Solid carriers, which may be used for dusts, wettable powders, water dispersible granules, or granules, may be mineral fillers, such as calcite, talc, kaolin, montmorillonite or attapulgite. The physical properties may be improved by addition of highly dispersed silica gel or Polymers. Carriers for granules may be porous material, e.g. pumice, kaolin, sepiolite, bentonite; non-sorptive carriers may be calcite or sand. Additionally, a multitude of pregranulated inorganic or organic materials may be used, such as dolomite or crushed plant residues.
Pesticidal compositions are often formulated and transported in a concentrated form which is subsequently diluted by the user before application. The presence of small amounts of a carrier which is a surfactant facilitates this process of dilution. Thus, preferably at least one carrier in a composition according to the Invention is a surfactant. For example, the composition may contain at two or more carriers, at least one of which is a surfactant.
Surfactants may be nonionic, anionic, cationic or zwitterionic substances with good dispersing, emulsifying and wetting properties depending an the nature of the compound according to general formula I to be formulated. Surfactants may also mean mixtures of individual surfactants
The compositions of the Invention may for example be formulated as wettable powders, water dispersible granules, dusts, granules, tablets, solutions, emulsifiable concentrates, emulsions, suspension concentrates and aerosols. Wettable powders usually contain 5 to 90% w/w of active ingredient and usually contain in addition to solid inert carrier, 3 to 10% w/w of dispersing and wetting agents and, where necessary, 0 to 10% w/w of stabilizer(s) and/or other additives such as penetrants or stikkers. Dusts are usually formulated as a dust concentrate having a similar composition to that of a wettable powder but without a dispersant, and may be diluted in the field with further solid carrier to give a composition usually containing 0.5 to 10% w/w of active ingredient. Water dispersible granules and granules are usually prepared to have a size between 0.15 mm and 2.0 mm and may be manufactured by a variety of techniques. Generally, these types of granules will contain 0.5 to 90% w/w active ingredient and 0 to 20% w/w of additives such as stabilizer, surfactants, slow release modifiers and binding agents. The so-called xe2x80x9cdry flowablesxe2x80x9d consist of relatively small granules having a relatively high concentration of active ingredient. Emulsifiable concentrates usually contain, in addition to a solvent or a mixture of solvents, 1 to 80% w/v active ingredient, 2 to 20% w/v emulsifiers and 0 to 20% w/v of other additives such as stabilizers, penetrants and corrosion inhibitors. Suspension concentrates are usually milled so as to obtain a stable, nonsedimenting flowable product and usually contain 5 to 75% w/v active ingredient, 0.5 to 15% w/v of dispersing agents, 0.1 to 10% w/v of suspending agents such as protective colloids and thixotropic agents, 0 to 10% W/v of other additives such as defoamers, corrosion inhibitors, stabilizers, penetrants and stickers, and water or an organic liquid in which the active ingredient is substantially insoluble; certain organic solids or inorganic salis may be present dissolved in the formulation to assist in preventing sedimentation and crystalization or as antifreeze agents for water. Aqueous dispersions and emulsions, for example compositions obtained by diluting the formulated product according to the Invention with water, also lie within the scope of the invention.
Of particular interest in enhancing the duration of the protective activity of the compounds of this Invention is the use of a carrier which will provide slow release of the pesticidal compounds into the environment of a plant which is to be protected.
The biological activity of the active ingredient can also be increased by including an adjuvant in the spray dilution. An adjuvant is defined here as a substance which can increase the biological actively of an active ingredient but is not itself significantly biologically active. The adjuvant can Bither be included in the formulation as a coformulant or carrier, or can be added to the spray tank together with the formulation containing the active ingredient.
As a commodity the compositions may preferably be in a concentrated form whereas the end user generally employs diluted compositions. The compositions may be diluted to a concentration down to 0.001% of active ingredient. The doses usually are in the range from 0.01 to 10 kg a.i./ha.
Examples of formulations according to the Invention are:
The compositions of this invention can be applied to the plants or their environment simultaneous with or in succession with other active substances. These other active substances can be Bither fertilisers, agents which donate trace elements or other preparations which influence plant growth. However, they can also be selective herbicides, insecticides, fungicides, bactericides, nematicides, algicides, molluscicides, rodenticides, virucides, compounds inducing resistance into plants, biological control agents such as viruses, bacteria, nematodes, fungi and other microorganisms croorganisms, repellents of birds and animals, and plant growth regulators, or mixtures of several of these preparations, if appropriate together with other carrier substances conventionally used in the art of formulation, surfactants or other additives which promote application.
Furthermore, the other pesticide can have a synergistic effect anthe pesticidal activity of the compound of formula I. The other fungicidal compound can be, for example, one which is also capable of combating diseases of cereals (e.g. wheat) such as those caused by Erysiphe, Puccinia, Septoria, Gibberella and Helminthosporium spp., seed and soil Borne diseases and downy and powdery mildews an eines, early and late blight an solanaceous crops, and powdery mildew and scab an apples etc. These mixtures of fungicides can have a broader spectrum of activity than the compound of general formula I alone. Furthermore, the other fungicide can have a synergistic effect an the fungicidal activities of the compound of formula I.
Examples of the other fungicidal compounds are anilazine, azoxystrobin, benalaxyl, benomyl, binapacryl, bitertanol, blasticidin S, Bordeaux mixture, bromuconazole, bupirimate, captafol, captan, carbendazim, carboxin, carpropamid, chlorbenzthiazon, chlorothalonil, chlozolinate, copper-containing compounds such as copper oxychloride, and copper sulfate, cycloheximide, cymoxanil, cypofuram, cyproconazole, cyprodinil, dichlofluanid, dichlone, dichloran, diclobutrazol, diclocymet, diclomezine, diethofencarb, difenoconazole, diflumetorim, dimethirimol, dimethomorph, diniconazole, dinocap, ditalimfos, dithianon, dodemorph, dodine, edifenphos, epoxiconazole, etaconazole, ethirimol, etridiazole, famoxadone, fenapanil, fenamidone, fenarimol, fenbuconazole, fenfuram, fenhexamid, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fentin, fentin acetate, fentin hydroxide, ferimzone, fluazinam, fludioxonil, flumetover, fluquinconazole, flusilazole, flusulfamide, flutolanil, flutriafol, folpet, fosetylaluminium, fuberidazole, furalaxyl, furametpyr, guazatine, hexaconazole, IKF-916, imazalil, iminoctadine, ipconazole, iprodione, isoprothiolane, iprovalicarb, kasugamycin, KH-7281, kitazin P, kresoximmethyl, mancozeb, maneb, mepanipyrim, mepronil, metalaxyl, metconazole, methfuroxam, MON 65500, myclobutanil, neoasozin, nicket dimethyldithiocarbamate, nitrothalisopropyl, nuarimol, ofurace, organo mercury compounds, oxadixyl, oxycarboxin, penconazole, pencycuron, phenazineoxide, phthalide, polyoxin D, polgram, probenazole, prochloraz, procymidione, propamocarb, propiconazole, propineb, pyraclostrobin, pyrazophos, pyrifenox, pyrimethanil, pyroguilon, pyroxyfur, quinomethionate, quinoxyfen, quintozene, spiroxamine, SSF-126, SSF-129, streptomycin, sulfur, tebuconazole, tecloftalame, tecnazene, tetraconazole, thiabendazole, thifluzamide, thiophanate-methyl, thiram, tolclofosmethyl, tolylfluanid, triadimefon, triadimenol, triazbutil, triazoxide, tricyclazole, tridemorph, trifloxystrobin, triflumizole, triforine, triticonazole, validamycin A, vinclozolin, XRD-563, zarilamid, zineb, ziram.
In addition, the co-formulations according to the Invention mag contain at least one compound of formula I and any of the following classes of biological control agents such as viruses, bacteria, nematodes, fungi, and other microorganisms which are suitable to control insects, weeds or plant diseases or to induce holt resistance in the plants. Examples of such biological control agents are: Bacillus thuringiensis, Verticillium lecanu, Autographica californica NPV, Beauvaria bassiana, Ampelomyces quisqualis, Bacilis subtilis, Pseudomonas chlororaphis, Pseudomonas fluorescens, Steptomyces griseoviridis and Trichoderma harzianum. 
Moreover, the co-formulations according to the Invention mag contain at least one compound of formula I and a chemical agent that induces the systemic acquired resistance in plants such as for example isonicotinic acid or derivatives thereof, 2,2-dichloro-3,3-dimethylcyclopropanecarboxylic acid or BION.
The compounds of formula I can be mixed with soil, peat or other rooting media for the protection of the plants against seed-Borne, soilborne or foliar fungal diseases.
The Invention still further provides the use as a fungicide of a compound of the formula I as defined above or a composition as defined above, and a method for combating fungus at a locus, which comprises treating the locus, which may be for example plants subject to or subjected to fungal attack, seeds of such plants or the medium in which such plants are growing or are to be grown, with such a compound or composition.
The present Invention is of wide applicability in the protection of crop and ornamental plants against fungal attack. Typical crops which may be protected include eines, grain crops such as wheat and barley, rice, sugar Beet, top fruit, peanuts, potatoes, vegetables and tomatoes. The duration of the protection is normally dependent an the individual compound selected, and also a variety of external factors, such as climate, whose Impact is normally mitigated by the use of a suitable formulation.
With due modification of the starting compounds, the protocols shown in the synthesis examples below were used for obtaining further compounds I. The resulting compounds, together with physical data, are listed in the Tables which follow.